rs9535307

chr13-49717706-A-Cchr13-49717706-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002267.4(KPNA3):c.771+2069T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 152,116 control chromosomes in the GnomAD database, including 54,575 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.85 (54575 hom., cov: 32)
• Consequence: KPNA3 NM_002267.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334

Genes affected

KPNA3 (HGNC:6396): (karyopherin subunit alpha 3) The transport of molecules between the nucleus and the cytoplasm in eukaryotic cells is mediated by the nuclear pore complex (NPC), which consists of 60-100 proteins. Small molecules (up to 70 kD) can pass through the nuclear pore by nonselective diffusion while larger molecules are transported by an active process. The protein encoded by this gene belongs to the importin alpha family, and is involved in nuclear protein import. [provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KPNA3	NM_002267.4	c.771+2069T>G		intron_variant		ENST00000261667.8
KPNA3	XM_017020561.2	c.699+2069T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KPNA3	ENST00000261667.8	c.771+2069T>G		intron_variant		1	NM_002267.4	P1

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128463 AN: 151998 Hom.: 54526 Cov.: 32

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.867

Gnomad OTH AF: 0.830

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.845 AC: 128570 AN: 152116 Hom.: 54575 Cov.: 32 AF XY: 0.847 AC XY: 62974 AN XY: 74342

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.874

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.924

Gnomad4 FIN AF: 0.846

Gnomad4 NFE AF: 0.867

Gnomad4 OTH AF: 0.832

Alfa AF: 0.860 Hom.: 17531

Bravo AF: 0.846

Asia WGS AF: 0.946 AC: 3287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.60
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9535307; hg19: chr13-50291842;